Rejuvenating senescent and centenarian human cells by reprogramming through the pluripotent state

Direct reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) provides a unique opportunity to derive patient-specific stem cells with potential applications in tissue replacement therapies and without the ethical concerns of human embryonic stem cells (hESCs). However, cellular...

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Bibliographic Details
Published in:Genes & development 2011-11, Vol.25 (21), p.2248-2253
Main Authors: Lapasset, Laure, Milhavet, Ollivier, Prieur, Alexandre, Besnard, Emilie, Babled, Amelie, Aït-Hamou, Nafissa, Leschik, Julia, Pellestor, Franck, Ramirez, Jean-Marie, De Vos, John, Lehmann, Sylvain, Lemaitre, Jean-Marc
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Animals
Cell Differentiation
Cell Line
Cells, Cultured
Cellular Reprogramming
Cellular Senescence - drug effects
Cellular Senescence - genetics
Genetics
Humans
Induced Pluripotent Stem Cells - cytology
Life Sciences
Mice
Mice, Inbred NOD
Mice, SCID
Mitochondria - metabolism
Rejuvenation
Research Communication
Telomere - genetics
Telomere - metabolism
Transcription Factors - pharmacology
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Summary:Direct reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) provides a unique opportunity to derive patient-specific stem cells with potential applications in tissue replacement therapies and without the ethical concerns of human embryonic stem cells (hESCs). However, cellular senescence, which contributes to aging and restricted longevity, has been described as a barrier to the derivation of iPSCs. Here we demonstrate, using an optimized protocol, that cellular senescence is not a limit to reprogramming and that age-related cellular physiology is reversible. Thus, we show that our iPSCs generated from senescent and centenarian cells have reset telomere size, gene expression profiles, oxidative stress, and mitochondrial metabolism, and are indistinguishable from hESCs. Finally, we show that senescent and centenarian-derived pluripotent stem cells are able to redifferentiate into fully rejuvenated cells. These results provide new insights into iPSC technology and pave the way for regenerative medicine for aged patients.
ISSN:0890-9369
1549-5477
DOI:10.1101/gad.173922.111